170,190 research outputs found
The complement system at the embryo implantation site
No full textThe Complement (C) system plays an important role in the control of infectious agents and in the removal of immune complexes and apoptotic cells. Like other components of innate immunity, C is able to recognize the targets through the early components and to attack them through the biologically active products released as a result of activation.
While recognition is restricted to harmful agents, the effector phase associated with the activation products of the terminal components is not selective for foreign targets and may also attack host cells. Thus, C can be considered an effective defence system but also a potential danger that may differently affect various tissues and organs.
The protective function of the C system is particularly important during pregnancy since the implanted embryo is vulnerable to attack by pathogens that colonize the cervico-vaginal cavity. Uncontrolled complement activation is prevented in successful pregnancy by the regulatory proteins positioned on the surface of several placental cells, however, unrestricted C activation induced by antibody-dependent and independent mechanisms may overcome the neutralizing effect of the C inhibitors and results in tissue damage and poor pregnancy outcome.
C components produced at feto-maternal interface serve an important function in placental development. C1q synthesized by decidual endothelial cells and expressed on the cell surface is particularly important in this regard because it acts as a molecular bridge between endovascular trophoblast and endothelial cells. C1q is also produced by trophoblast and is used to favour trophoblast migration through the decidua. Defective expression of C1q by trophoblast is associated with impaired trophoblast invasion of decidua and may have important implications in pregnancy disorders such as preeclampsia characterized by reduced vascular remodeling.
In conclusion the C system behaves as a double-edged sword, exerting a protective function and inducing damage in pathological situations that may result in poor pregnancy outcome
The complement component C3 is expressed by the endometrial ectopic tissue and is involved in the endometriotic lesion formation
No full textOP28
The complement component C3 is expressed by the
endometrial ectopic tissue and is involved in the
endometriotic lesion formation
C. Agostinis 1, G. Zito 1, D. De Santo1, R. Vidergar2,
O. Radillo 1, F. Bossi 1, S. Zorzet2, G. Ricci 1,
R. Bulla 2
1 Institute for Maternal and Child Health, IRCCS
Burlo Garofolo, Trieste, Italy
2 Department of Life Sciences, University of Trieste,
Trieste, Italy
E-mail address: [email protected] (C. Agostinis).
Background: The complement (C) system is one of the major
components of humoral innate immunity, acting as the first lines
of defence against microbes. The principal roles of C system are the
opsonization and lysis of pathogens, but new roles in inflammatory
and immunological processes are emerging. It is involved in numerous
inflammatory diseases, such as SLE, PNH and endometriosis
(EM).
Several groups have been demonstrated that the glandular
epithelial cells found in endometriotic implants produce and
secrete the C component C3. The aim of this work was to confirm
the presence of C3 the in the ectopic tissue compared to the eutopic
one, and investigate the role of C3 in the pathogenesis of EM.
Methods:Weinvestigated by immunofluorescence, the expression
of C3 on sections of endometriotic cysts and healthy uterus;
we performed RT-qPCR experiments to highlight the synthesis of
this C component at local level. We set up a murine in vivo model
of endometriosis based on the injection of minced uterine tissue
from a donor mouse, into the peritoneum of a receiving animal.
Results: We confirmed the presence of C3 selectively in the
ectopic and not in eutopic endometrium, and the local synthesis
of C3 in endometriotic tissue. We observed a greater amount of
cyst formation in the peritoneum of WT mice compared to C3 KO
mice.Conclusion: We concluded that C3 can actually be considered a
marker of EM and that the local synthesis of this C component can
promote the engraftment of the cysts
The Rise and Fall of IIRSA and the Prospects for Regional Infrastructure Integration in the Post-Pandemic.
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Review of the book Comparative Regional Integration. Governance and Legal Models. By C. Closa & L. Casini (eds.)
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COVID-19, Pre-Eclampsia, and Complement System
No full textCopyright © 2021 Agostinis, Mangogna, Balduit, Aghamajidi, Ricci, Kishore and Bulla. COVID-19 is characterized by virus-induced injury leading to multi-organ failure, together with inflammatory reaction, endothelial cell (EC) injury, and prothrombotic coagulopathy with thrombotic events. Complement system (C) via its cross-talk with the contact and coagulation systems contributes significantly to the severity and pathological consequences due to SARS-CoV-2 infection. These immunopathological mechanisms overlap in COVID-19 and pre-eclampsia (PE). Thus, mothers contracting SARS-CoV-2 infection during pregnancy are more vulnerable to developing PE. SARS-CoV-2 infection of ECs, via its receptor ACE2 and co-receptor TMPRSS2, can provoke endothelial dysfunction and disruption of vascular integrity, causing hyperinflammation and hypercoagulability. This is aggravated by bradykinin increase due to inhibition of ACE2 activity by the virus. C is important for the progression of normal pregnancy, and its dysregulation can impact in the form of PE-like syndrome as a consequence of SARS-CoV-2 infection. Thus, there is also an overlap between treatment regimens of COVID-19 and PE. C inhibitors, especially those targeting C3 or MASP-2, are exciting options for treating COVID-19 and consequent PE. In this review, we examine the role of C, contact and coagulation systems as well as endothelial hyperactivation with respect to SARS-CoV-2 infection during pregnancy and likely development of PE.Ferring COVID-19 Investigational Grant (GRAVISAR to RB); Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy (RC24/19 to GR and 09/21 to CA)
C1q secreted in the tumour microenvironment promotes tumour growth in the absence of complement activation
No full textWe have recently shown that locally secreted C1q is involved in trophoblast invasion of decidua during pregnancy (Agostinis
et al., J. Immunol. 2010;185;4420–4429). Since this physiologic process resembles to some extent tumor progression, we sought
to investigate if C1q plays a similar role in tumor development and progression. Immunohistochemical analysis of several solid
tumours including colon, prostate, lung and breast cancer and melanoma revealed the presence of C1q that was localized on the
vascular endothelium and also distributed in the stroma in the absence of C4. To investigate the in vivo role of C1q in tumour
development, 6/8 week old female WT and C1q−/− C57BL/6 mice received an intramuscular injection of 0.5×105 B16/F10 melanoma
cells. The tumour mass measured daily for 2 weeks was significantly reduced in C1q−/− mice compared with WT animals and the
survival of complement deficient mice was significantly prolonged. Interestingly, the tumor growth of B16 melanoma syngeneic model
established in C3 and C5−/− mice and the survival rate of tumorbearing C3 and C5 deficient mice were not significantly different
from those observed in WT mice. C1q was detected by immunofluorescence analysis on the vessel endothelium and in the stroma of
the tumor mass in WT mice in the absence of C4 and C3. The vessel density both inside the tumor mass and in the peritumoral area
evaluated by CD34 staining was similar in WT and C1q−/− animals and no difference was observed in the percentage of cell types of
tumour infiltrating leucocytes examined by FACS analysis in the two groups of mice. In vitro experiments were also performed to
analyse the mechanism of C1q-mediated tumor growth. C1q was found to promote adhesion and migration of melonoma cells, but
failed to induce cell proliferation. In conclusion, our data suggest that C1q present in the tumour microenvironment may contribute
to tumor growth via a mechanism independent on complement activation
USE DE 2,4-DIHALO-6-SUBSTITUIDO-1-3, 5-TRAZINAS E SEUS DERIVADOS COMO AGENTES DE CONDENSAçÃO, RETICULAçÃO, BRONZEAMENTO, ENXERTO E CURA
No full textUse of 2,4-dihalo-6-substituted-1,3,5-triazines as condensing., cross-linkinf, tanning, grafting, curing agents for the production of amides, esters, thioesters, and stabilized collagen and leather, CMC (carboxymethyl cellulose), synthetic and natural polymers. The process enables to obtain non-toxic and totally free of heavy metals products characterized by Tg values between 80°C and 100°C
Analysis of anti-C1q antibodies in normal and pathological pregnancies
No full textAnalysis of anti-C1q antibodies in normal and pathological pregnancies
C. Agostinis1, A. Mangogna2, O. Radillo1, G. Ricci1, R. Bulla2.
1. Institute for Maternal and Child Health, IRCCS Burlo Garofolo, 34137, Trieste, Italy;
2. Department of Life Sciences, University of Trieste, 34127, Trieste, Italy.
PROBLEM
C1q, the recognition molecule of the classical pathway of the complement system plays foundamental roles in pregnancy. C1q has been shown to promote trophoblast endovascular and interstitial invasion and is involved in the clearance of immune complexes and apoptotic bodies. Lack of C1q is characterized by poor trophoblast invasion and pregnancy failure.
This molecule can be also the target of an antibody response: anti‐C1q antibodies are present in several infectious and autoimmune diseases. The presence of these auto-antibodies has been detected also in 2 to 8% of the general population.
The aim of this study was to evaluate the presence and the circulating levels of anti-C1q Ab in pre-eclamptic (PE) patients compared to healthy pregnant women.
METHOD
Levels of anti‐C1q antibodies were analyzed by ELISA in PE and control sera obtained in the first and third trimester of pregnancy.
RESULTS
Anti-C1q antibodies were detected in both normal and PE sera. Higher levels of these antibodies were present in the first trimester compared to term normal pregnant sera. Early onset PE patients showed higher levels of anti-C1q antibodies compared to late onset PE patients.
CONCLUSION
Anti-C1q antibody levels increased during the first trimester of pregnancy. The level of these antibodies was higher in the sera of some early onset PE patients. These data indicates a possible role of anti-C1q antibodies in the control of pregnancy and in the pathogenesis of PE. The role played by these antibodies at foeto-maternal interface requires further investigation
Beyond the Norm: The emerging interplay of complement system and extracellular matrix in the tumor microenvironment
No full textGround-breaking awareness has been reached about the intricate and dynamic connection between developing tumors and the host immune system. Being a powerful arm of innate immunity and a functional bridge with adaptive immunity, the complement system (C) has also emerged as a pivotal player in the tumor microenvironment (TME). Its “double-edged sword” role in cancer can find an explanation in the controversial relationship between C capability to mediate tumor cell cytolysis or, conversely, to sustain chronic inflammation and tumor progression by enhancing cell invasion, angiogenesis, and metastasis to distant organs. However, comprehensive knowledge about the actual role of C in cancer progression is impaired by several limitations of the currently available studies. In the current review, we aim to bring a fresh eye to the controversial role of C in cancer by analyzing the interplay between C and extracellular matrix (ECM) components as potential orchestrators of the TME. The interaction of C components with specific ECM components can determine C activation or inhibition and promote specific non-canonical functions, which can, in the tumor context, favor or limit progression based on the cancer setting. An in-depth and tumor-specific characterization of TME composition in terms of C components and ECM proteins could be essential to determine their potential interactions and become a key element for improving drug development, prognosis, and therapy response prediction in solid tumors
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